Cisplatin
Platinol · Platinum agent
Proximal tubular ATN + magnesium wasting; the archetype.
ATNLYTEPRE
SevereOpen →
Immunomodulatory drug (IMiD)
Lenalidomide
Revlimid · LEN
A renally cleared immunomodulatory drug where dose adjustment by CrCl is central and AKI, Fanconi, and tumor flare can complicate kidney care.
ModerateImmunomodulatory drug (IMiD) · approved 2005
Multiple myelomaMyelodysplastic syndrome with del(5q)Mantle cell lymphomaFollicular and marginal zone lymphoma
Signature kidney injury
Acute Tubular Necrosis
AKI/azotemia is uncommon but recognized, described mainly in case series of plasma-cell dyscrasias with underlying renal insufficiency; not reliably quantified as an incidence. Rare Fanconi syndrome and TMA are reported. Because ~80% of lenalidomide is renally cleared as unchanged drug, accumulation in renal impairment is the dominant driver of toxicity, including myelosuppression.
Source: Batts et al., Leuk Lymphoma 2008; PK Chen et al., J Clin Pharmacol 2007
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityModerate
ReversibilityVariable
Evidence0 refs
Nephron map
Glomerulus
Vasculature / Endothelium
Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water
Interstitium
Acute Tubular Necrosis
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Mechanism of kidney injury
Mechanisms are incompletely defined. Lenalidomide is eliminated predominantly by glomerular filtration and renal tubular secretion as unchanged drug, so reduced clearance in CKD raises systemic exposure (AUC increased ~185-420% across moderate-to-severe impairment) and amplifies toxicity. Proposed renal-specific contributors include proximal tubular injury (occasionally a Fanconi pattern with phosphate and amino-acid wasting), the combined nephrotoxic burden of paraproteins plus an anti-angiogenic agent, and rarely tumor flare/tumor lysis and TMA.
Clinical presentation
Rising creatinine/azotemia, sometimes progressing to dialysis; rare proximal tubular dysfunction (glucosuria with normoglycemia, hypophosphatemia, aminoaciduria) or TMA features (schistocytes, thrombocytopenia). Tumor flare may present with painful lymphadenopathy and rising LDH early in CLL/lymphoma treatment.
Onset
Variable; azotemia reported from weeks to several months after initiation.
Reversibility
Variable
Anticancer mechanism
Thalidomide analogue that binds cereblon to redirect the CRL4 E3 ubiquitin ligase, triggering ubiquitination and proteasomal degradation of the transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos); this produces direct antimyeloma, anti-angiogenic, and T/NK-cell immunostimulatory effects. Used in multiple myeloma, del(5q) MDS, and certain lymphomas.
Management
Hold or dose-reduce for AKI and treat reversible contributors (volume, paraprotein, nephrotoxins); monitor renal function and electrolytes. Some cases are irreversible and require dialysis, so early recognition and CrCl-based dose adjustment are essential. For TMA, stop the drug and manage supportively.
Risk factors
- Pre-existing renal insufficiency (drives exposure and toxicity)
- Plasma-cell dyscrasia with nephrotoxic paraproteins
- Fixed (non-adjusted) dosing in reduced renal function
- High tumor burden (tumor flare/lysis)
Prevention
- Adjust starting dose to creatinine clearance (see dosing)
- Monitor renal function and CBC closely after initiation
- Maintain hydration; tumor-lysis precautions in high-burden disease
Note · Renally cleared - dose adjustment by creatinine clearance is central. AKI incidence is not well quantified and is described at the case-series level.
Clinical depth
Renal dose adjustment
Per pharmacokinetic data, adjust the starting dose when CrCl <60 mL/min (myeloma labeling): CrCl 30-60 use ~10 mg daily; CrCl <30 not on dialysis use 15 mg every other day; on dialysis use 5 mg once daily, given after dialysis on dialysis days. Disease-specific labels differ; titrate to tolerance.
Dialyzability & ESKD dosing
Yes, lenalidomide is removed by hemodialysis - a 4-hour session cleared ~31% of body drug content. Administer the daily dose after the dialysis session on dialysis days.
Differential diagnosis
Separate drug accumulation/ATN from myeloma cast nephropathy (look for the paraprotein and free light chains), from prerenal azotemia (volume responsive), and from rare lenalidomide TMA (MAHA triad). A Fanconi pattern (normoglycemic glucosuria, phosphaturia, LMW proteinuria) points to proximal tubular toxicity.
Monitoring
- Serum creatinine/CrCl at baseline and before dose escalation
- CBC (cytopenias track exposure) at least monthly
- Electrolytes including phosphate if tubular dysfunction suspected
- Tumor-lysis labs early in high-burden disease
Key trials & series
- Chen et al. renal-impairment pharmacokinetic/hemodialysis study (J Clin Pharmacol 2007)
- Batts et al. azotemia case series (Leuk Lymphoma 2008)
Clinical pearls
- Lenalidomide is renally cleared - always dose by CrCl and give after dialysis; failing to adjust causes both cytopenias and worsening renal function.
- Unlike pomalidomide, lenalidomide exposure rises sharply in CKD, so the two IMiDs are not interchangeable in renal impairment.
- New thrombocytopenia plus AKI on lenalidomide should prompt a smear to exclude TMA.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Interstitium
Supporting tissue around the tubules
Injury signatures
Acute Tubular NecrosisFanconi SyndromeThrombotic Microangiopathy
Beyond the kidney
Class-level context for the major non-renal toxicities of immunomodulatory drug (imid)s.
Vascular
Hypertension, VTE/ATE, bleeding, aneurysm
- Venous thromboembolism
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Neuropathy (thalidomide)
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkAzotemia associated with use of lenalidomide in plasma cell dyscrasias.Batts ED et al. · Leuk Lymphoma 2008 · PMID 18452093Case series of progressive azotemia (including a Fanconi-syndrome patient) on lenalidomide.PMIDPharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis.Chen N et al. · J Clin Pharmacol 2007 · PMID 17954615Defines the renal clearance of lenalidomide, the AUC rise in CKD, hemodialysis removal (~31%), and the basis for dose adjustment.PMIDPomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials.Siegel DS et al. · Leuk Lymphoma 2016 · PMID 27267105Contrasts renal clearance of lenalidomide with pomalidomide in renal impairment.PMIDLenalidomide and chronic lymphocytic leukemia.Gonzalez-Rodriguez AP et al. · Biomed Res Int 2013 · PMID 24163824Reviews lenalidomide toxicity including tumor lysis and tumor flare reaction.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onco-nephrology review of newer anticancer-agent renal effects, including immunomodulatory and targeted drugs.PMIDPharmacological nephrotoxicity profile in a comprehensive cancer center: What changed in two decades and predictors for the need for haemodialysis and mortality.Ferreira A et al. · Nefrologia (Engl Ed) 2025 · PMID 40783302Cancer-center AKI series contextualizing drug-induced AKI requiring dialysis in hematologic malignancy.